PloS one · 2009
Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gabrielli Elena, Pericolini Eva, Cenci Elio, Ortelli Federica, Magliani Walter, Ciociola Tecla, Bistoni Francesco, Conti Stefania, Vecchiarelli Anna, Polonelli Luciano
Аннотация
BACKGROUND: It has been documented that, independently from the specificity of the native antibody (Ab) for a given antigen (Ag), complementarity determining regions (CDR)-related peptides may display differential antimicrobial, antiviral and antitumor activities.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we demonstrate that a synthetic peptide with sequence identical to V(H)CDR3 of a mouse monoclonal Ab (mAb) specific for difucosyl human blood group A is easily taken up by macrophages with subsequent stimulation of: i) proinflammatory cytokine production; ii) PI3K-Akt pathway and iii) TLR-4 expression. Significantly, V(H)CDR3 exerts therapeutic effect against systemic candidiasis without possessing direct candidacidal properties.
CONCLUSIONS/SIGNIFICANCE: These results open a new scenario about the possibility that, beyond the half life of immunoglobulins, Ab fragments may effectively influence the antiinfective cellular immune response in a way reminiscent of regulatory peptides of innate immunity.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we demonstrate that a synthetic peptide with sequence identical to V(H)CDR3 of a mouse monoclonal Ab (mAb) specific for difucosyl human blood group A is easily taken up by macrophages with subsequent stimulation of: i) proinflammatory cytokine production; ii) PI3K-Akt pathway and iii) TLR-4 expression. Significantly, V(H)CDR3 exerts therapeutic effect against systemic candidiasis without possessing direct candidacidal properties.
CONCLUSIONS/SIGNIFICANCE: These results open a new scenario about the possibility that, beyond the half life of immunoglobulins, Ab fragments may effectively influence the antiinfective cellular immune response in a way reminiscent of regulatory peptides of innate immunity.
Предметные рубрики MeSH
Adaptive ImmunityAnimalsAntifungal AgentsCandida albicansCandidiasisComplementarity Determining RegionsEnzyme ActivationHumansImmunity, InnateImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionImmunomodulationMacrophages, PeritonealMiceNeutrophilsPeptidesProto-Oncogene Proteins c-aktSurvival AnalysisToll-Like Receptor 4Tumor Necrosis Factor-alphaUp-Regulation